Tdbasicsem

TOPOLOGICAL PROCESS DYNAMICS
and
Applications to Biosystems
{Basic outline material for a seminar(series) on the theme of topological process dynamics in
quantum physics and with extensions and applications in biophysics and structural biology)

M. Dudziak

January 30, 1998

MJD 1 16-02-07 2:41 PM

Outline of the Seminar
1. Introduction

2. Overview of Topological Dynamics – Quantum, Geometry, and Biosystem

3. P-Adic Numbers and Length Scales

4. The “CHAOITON” Project with JINR and Topologically Stable Solitons

5. A Critical Hypothesis for Biosystems and the Brain

6. Experimental Foundations and Earlier Scanning Probe Microscopy Studies

7. QNET and CLANS – Early Computational Simulations

8. A New Experimental Approach Based Upon Magneto-Optic Sensors and Controllers

9. Recapitulation and Conclusions
(1a)

MJD 2 16-02-07 2:41 PM

1. INTRODUCTION
Motivating Questions and Issues

Is there a problem with our fundamental view of space and time?

Consider EPR and non-locality and the Quantum Potential (Bohm, Hiley, 1980’s)

There may be only certain allowable (probabilistic) spacetimes and some of them
give rise to the dominant (measured) spacetime we call the universe

Are there only certain allowable or critical geometries and length scales that
govern transitions between one spacetime process and another?

Things may be discretized, and the analytics may be fractal-like or p-adic.

What kind of connection may exist between quantum events and biological
structures and processes, in the brain or elsewhere? (1b, 1c)

MJD 3 16-02-07 2:41 PM

Figures 1.1, 1.2 – pages from B&H with AB effect trajectory and QP for AB effect

MJD 4 16-02-07 2:41 PM

1.1 (aux)

Page with generalized Schröd. wave eq. and QP eqs. (p. 21 from 9/95 talk)

MJD 5 16-02-07 2:41 PM

1(a)
The plan is to describe briefly some theoretical foundations that bring a new orientation to the role of surfaces and
multiple 3-spaces at the quantum scale but also at macroscopic scales and in particular for biological systems.

The basis for this approach, called Topological Process Dynamics or Topological Geometrodynamics, is in a view
of physical spacetimes (plural) as surfaces in a higher dimensional structure, wherein there is a hierarchy of sheets,
as it were, communicating or exchanging energy only at specific points or wormholes (M. Pitkanen, Helsinki).
[Note origin of TGD term, fundamentals with MP, references, etc.]

The metric of this complex space H is related to p-adic numbers which come into the picture above Planck length
scales. There are implications for hadron string physics and potentially for biology.

The basic p-Adic length scale hypothesis predicts that primes near prime powers of two correspond to physically
important length scales:

L(p) = sqrt(p)*L0, p about 2k, k prime, or a power of a prime.
L0 about 104 Planck lengths.

Indeed, k=132=169 is a power of prime and provides the best fit to
neutrino mass squared differences and corresponds also to the length scale
associated with the so-called epithelial sheets in the biosystems.

MJD 6 16-02-07 2:41 PM

1(b)
Next we will look at the approaches begun first at VCU for two objectives –

First, on the theoretical side, we began to study stability and behavior of 1-D and 1+1 solitons, with colleagues at
JINR in Russia, since these were seen as offering some promise for a mechanism by which chaotic and entangled
events at the quantum level could give rise to behaviors analogous to elementary particles. The rationale was that,
with other evidence of critical soliton-like activity at the macromolecular level (proteins, DNA), this might be a
mechanism, and certainly interesting in its own right.

Second, we attempted to define and construct both an experimental platform and computer simulations (against
which to compare experimental results and thereby, iteratively, work towards a mathematical model) for
investigating how these soliton and biosoliton phenomena could manifest in real biology. The focus was upon
neurons and their cytoskeletal and synapto-dendritic geometries, because of a tradition of speculation going back to
Eccles, Umezawa, Del Guidice, Stewart, Hameroff, and Penrose. Despite halts in the actual lab work this has led
to development of a new approach targeting bioelectromagnetic phenomena and the measurement of changes in
cytoskeletal and membrane structures in response to applied electromagnetic influences.

This research has in turn led to some very interesting results in magneto-optics pure and simple, several application
designs pertinent to the semiconductor and computing industry, and a new track in biomedical investigation that
hopefully will be underway by this summer.

Our goal remains to further develop the theoretical, mathematical foundations, but in the same time to push
forward on the applied science and actual real-world applications. The latter have been well compartmentalized
into applied R&D and product development.

MJD 7 16-02-07 2:41 PM

1(c)

Another Way of Rephrasing the Fundamental Motivating Questions

Why Is our Universe 3-Space?
(Or, why do we tend to experience everything in this way and not some other way?)

Why are there separable objects and processes in the first place?

Why did living systems develop in the geometry that it has?
(Why are things in a particular scaling system?)

What do complex systems work and survive while complicated non-complex ones do not?

Are computational models of the micro-universe and the cosmos merely interesting analogies
or is there something deeper?

MJD 8 16-02-07 2:41 PM

2. TOPOLOGICAL DYNAMICS
2.1 QUANTUM PROCESS
We begin with the notion of PROCESS as the source of structure and form

Process algebraic models (Clifford and Grassmann algebras) suggested as a way-out
to the problem of non-locality and the integration of QM and Gravity (Relativity)

Process Flux, Flow, Holomovement [Hiley, 1991]
Flow Features and Distinctions

Interdependence and potentiality ƒi = ƒ(ƒi-1) = ƒ(ƒ(ƒi-2)) ...
ƒ ƒƒ

Algebra of process

[P0P1] [P0P2]

[P0P3]

MJD 9 16-02-07 2:41 PM

2.2 [P0P1P0P2]

[P0P1P0P3]
[P0P1]
[P0P2]

[P0P3]

This can be rephrased as [a], [b], [c], [ab], [ac], [bc], such that
[ab][bc] = [ac], etc.

Identity processes [aa] = [bb] = [cc] = 1.

[ab][ba] = -[ab][ba] = -[aa] = -1, etc.

[abc][abc] = -[abc][acb] = [abc][cab] = [ab][ab] = -1

MJD 10 16-02-07 2:41 PM

2.3
This can be extended to Clifford and Pauli-Clifford algebras which are homomorphic to
the SO(3) Lie group of ordinary rotations.

The symplectic Clifford algebra can be generated by bosonic creation/annihilation
operators, but this is not about elementary particles but elements of fundamental process.

Picture a Quantum Geometry (Topology) from which a classical spacetime emerges as a
kind of statistical average:

MJD 11 16-02-07 2:41 PM

2.4
The POINT persists – it is an idempotent process, p p

Generation of points is accomplished by p1 = Tp0T-1 where T = translation operator

Motion (in the PROCESS view) is not a point-to-point sequence in time but an
INTEGRATION over a set of points in a phase space [Hiley & Fernandes, 1996]
(Similarities to Umezawa’s (1993) thermo field dynamics)

Points in classical space are related by some metric imposed from without:

pi+1 = (xi+1, yi+1, zi+1) = [ƒk(xi), ƒl(yi), (ƒm(zi)]

In quantum process, there are different relationships from the dynamics of the space as a
whole – a wave function may represent the movement in the vacuum state as a type of
thermally induced diffusion, of the form:

Ψ ( x, t ) = ∑ exp[− βE / 2]ΨE ( x) exp[−iEt / h ]
E

MJD 12 16-02-07 2:41 PM

2.5 GEOMETRODYNAMICS
Quantum Flux (Pre-SpaceTime) “Spin Glass” of 3-surface Regions (2a)

Planck-size 3-surfaces glued along boundaries by topological sum
sheets and hierarchies of scale

Basic spacetime concept (TGD, Pitkanen, 1985+) is to consider a 4D spacetime
surface in an 8D configuration space H = all 3-surfaces of M4+ x CP2 where

M4+ = 4D lightcone of Minkowski space and

CP2 = complex projective space of two complex dimensions.

z3=x3+iy3
λz
λz=λ’+iλ2
λ λ

z z2=x2+iy2
z1=x1+iy1

MJD 13 16-02-07 2:41 PM

2.6
Two aspects emerge – Poincare invariance of gravitation and a generalization
of the string model

Radical generalization of what is a 3-space (3-surface) – there are boundaries
and finite 3-spaces within (adjoining) others

Topologically trivial 3-space of GRT Topological Condensation and Evaporation

MJD 14 16-02-07 2:41 PM

2.7
Some Visualizations of Topological-Sum/Difference Particle Dynamics

MJD 15 16-02-07 2:41 PM

2.8
Topological Contacts and Condensation Leads to Hierarchies of Spacetime Sheets

MJD 16 16-02-07 2:41 PM

2.9
Joins along boundaries Strong Correlation among Quantum Systems
(A basis for macroscopic quantum systems and quantum coherence in biology)

MJD 17 16-02-07 2:41 PM

2.10
Kahler action of electromagnetic gauge flux between spacetime sheets occurs as a
charged WORMHOLE with characteristics of S2 x L.

Implication is that spacetime topology is ULTRAMETRIC below some length
scale(analogy to spin glass) such that

d ( x, y ) ≤ MAX (d ( x), d ( y )), ≠ (d ( x) + d ( y )

MJD 18 16-02-07 2:41 PM

2(a)
We start with a quantum process flux that is pre-space, pre-time, pre-form.
The question is how a stable spacetime with structure emerges from
Something that is No-Thing.

We move to the idea of a spin glass type behavior that is dynamically creating stable
vortices or eddies which are defining the elements of what the quantum and classical
world is built from. A kind of “virtual world” that is in fact the foundation of the
macroscopic “real” world.

These movements can be understood as topological transformations which are the
interactions of quantized component spaces with one another resulting in a continuous
manifold.

Extremals, fundamental 3-surfaces of Planck scale, can be thought of as fundamental
idempotent processes, but by joining and glueing with others at the same scale or higher
they give rise to sheets and geometries ultimately behaving at the classical order.

MJD 19 16-02-07 2:41 PM

3. P-ADIC NUMBERS AND LENGTH SCALES
3.1
Length Scale Hypothesis (3a)

L( p) ≈ 104 G p
Ordinary (real) topology approximates for above L(p), and spacetime sheets of
increasing size stay close to L(p).

P-Adicity

Let a real number
q = m/n = (r/s)pν

where r and s are relatively prime to each other and to p, s > 0

ϕp(q) = p-ν = p-adic valuation of q
and
|x|p = p-ν = p-adic absolute value of x

MJD 20 16-02-07 2:41 PM

3.2 From p-adic values to metrics (3a)

Every rational x has a “unique” p-adic expansion

∞
x = ∑ ajp j
j =m

where m=integer, aj=set of integers between 0 and p-1 inclusive, and sum convergent.

The p-adic metric d(x,y) = |x-y|p gives rise to the p-adic topology.

Spacetime surface Regions with different p-adic primes
(each corresponds to a sheet of finite size glued by wormhole contacts)

MJD 21 16-02-07 2:41 PM

3.3 Why a p-adic topology?

Kähler Action a type of nonlinear Maxwell field
that forms the configuration space geometry and associates unique X4(X3) to a given X3

K(X3) = Min {SK(X4) | X4 ⊃ X3}
(3a)
Vacuum degeneracy and nonequivalence

Something akin to spin glass state degeneracy

DISCONTINUOUS change of physical quantities through 3D surfaces
No Infinite Surface Energies
Like magnetization, but also in time dimension

Discontinuous time? (Suggested in another vein by Finkelstein (Chronons))

MJD 22 16-02-07 2:41 PM

3.4 How does the Length Hypothesis Work?

L(p) = sqrt(p) * L0

where L0 ≈ CP2 radius, @ 104 Planck length.

Elementary particle mass scales as 1/L(p), minimum size L(p)

Below L(p) p-adic physics, above real

FAVORED p-adic primes ≈ 2m, m=kn, k prime, n integer

Elementary particles (e, µ, τ)  k = 127, 113, 107 (3b)

Elementary Particle Horizon : P-Adic Minkowskian classical spacetime

MJD 23 16-02-07 2:41 PM

3.5

Lipid layers / cell membrane  k=149, 151

Typical cells  k=167

L = 2 (167−151) / 2 (10 −8 )m which is 2.56 ∗ 10 −6 m

Length scale k=157  Virus-sized structures

L = 2(157−151) / 2 (10 −8 )m which is 3.2 ∗10 −7 m

Length scale k=163  Nanobacteria structures [Kajander, 1997]

L = 2(163−151) / 2 (10 −8 )m which is 0.64 ∗ 10 −6 m

MJD 24 16-02-07 2:41 PM

Figure 3.1 – 3.4 from MP, TGD-PAD book (figures 2.2 – 2.5, chapter 2, pp. 44-47)

MJD 25 16-02-07 2:41 PM

3(a)
There are several factors involving p-adic numbers and metrics.
First there is the Quantum p-adicity below a minimum scale where p-adic topology
applies.

Space of minima of free energy is ultrametric, obeying N(x+y)<= Max(N(x), N(y))
& p-adic number are completion of rationals, one for each prime.

Second there is the p-adic length scale hypothesis and the relationships that seem to hold
between sizes of different spacetime sheets (particles, viruses, bacteria, cells, …
astronomical objects…)

(3.3) Consider all possible X4 with X3 as submanifold, X3 ⊂ X4. If X3 has a boundary
then it belongs to boundary of X4. Associate to each X4 the Kahler action which is
analogous to a minimum of thermodynamic free energy, changing discontinuously when
some config. space coordinate changes, a kind of phase transition or catastrophe action.

MJD 26 16-02-07 2:41 PM

3(b)
From M. Pitkanen, padic2.html:

Elementary particle masses are proportional to 1/sqrt(p) and hence exponentially
sensitive to the value of k. It is however possible to associate unique primes k to the
known elementary particles. For instance, electron, muon and tau correspond to the
subsequent (!) primes k=127,113,107.

Predictions are correct with few per cent and renormalization effects give an explanation
for the small discrepancies. TGD provides an explanation for CKM mixing as basically
due to the mixing of the boundary topologies of quark like 3-surfaces.

The requirement that CKM matrix satisfies empirical constraints fixes U and D matrices
and quark masses and leads to correct predictions for hadron masses. The scenario solves
also the spin crisis of proton and so called R_b and R_c anomalies of electroweak
standard model.

MJD 27 16-02-07 2:41 PM

4. “CHAOITON” – Chaotic Solitons in 1+ Dimensions
4.1

Independently we were noticing the phenomenon of solitons and their application to
elementary physics and to biological energy transport.

Could a soliton structure be at work providing STABILITY in topological processes
at different scales?

Could a soliton formalism in 3D model the type of wormhole gauge flux that would
sustain the topological identities and structures of spacetime 3-surface sheets in
condensation and evaporation processes?

Would such solitons be similar across particle physics, protein/DNA conformation,
and microtubule-constrained energy transport in cells?

First we had to examine whether certain apparent solitons were really non-trivial and
non-degenerate.

MJD 28 16-02-07 2:41 PM

4.2
Objective
Numerical and analytical investigation of particle-like soliton solutions :
Lorentz-invariant classical field theories
Broken internal symmetry,
Allowing for {D=1,2,3} topological solitons

Conjecture
3D particle-like solitons “built” of unit isovector, spinor, vector fields
in some type of classical approximation

Key Focus
Sigma-models – unit isovector n(x) field
Particle and nuclear physics Superfluid He phases
High-temp superconductivity Ferroelectrics and magnets
Macromolecule chains (DNA, protein)

MJD 29 16-02-07 2:41 PM

4.3
2D Sigma Model in Isotropic Heisenberg Antiferromagnet
Langragian
1
2
µ 1
2
2
[
L = ∂ µ sa ∂ sa = (∂ 0 sa ) − (∂ k sa )
2
]
with: sasa = 1 µ = 0, 1, 2 k = 1, 2 a = 1, 2, 3

Hamiltonian

H=
1
2
[
(∂ 0 sa )2 + (∂ k sa )2 ]
Time-dependent
( )
∂ µ ∂ µ si + ∂ µ sa ∂ µ sa si = 0, i = 1,2,3,

Stationary
∂ 2 si + (∂ k sa ) si = 0
2
k

MJD 30 16-02-07 2:41 PM

4.4

Using the (θ, φ) form of dynamic equations, we investigated Belavin-Polyakov (BP)
solitons:

m
r
θ s (r , R) = 2 arctan  , φ s = mχ
R
x y
r 2 = x 2 + y 2 , cos χ = , sin χ =
r r
Stationary topological BP solitons are stable independent of topological index Qt

Next question pair interactions under collisions.

Solitons in 2D anisotropic AFM differ from stationary BP solitons in isotropic AFM/FM
only by rotation in internal space at frequency ω.

We investigated x = 0, ω2 < 1, and ω2 = 1, and found dynamical topological solitons only
at ω2 = 1.

MJD 31 16-02-07 2:41 PM

Figures 4.1 – 4.9

Slides and transparencies of Sine-Gorden et al (MATLAB, etc.)

Fundamental Solitons
Sketches from book
Standard atan (2), Bell-type (2), Singularities (1)
Conjecture
What about weak instability?

MJD 32 16-02-07 2:41 PM

5. A Critical Hypothesis for Biology
5.1

Quantum Topological Events
Wormhole-like CP2 extremals operating between contiguous spacetime sheets
♦ occurring as type of CA or spin-glass phernomenon
♦ analogous to massively parallel computations
♦ superconductive pathways within phospholipid lattices

Generate 2D / 3D soliton behaviors that propagate through actin to MT networks

Create quasi-crystalline formations with intracellular and intercellular ranges

Acting as “quantum antennae” sensitive to minute changes and disturbances

Enabling quantum-scale coherence and superconductive signal propagation

MJD 33 16-02-07 2:41 PM

5.2
A Radical Hypothesis
Disturbing the Classical Reductionist (Non-Complex) Model

Disturbs the Standard Cell Biological Model including the Position of DNA and the
Nucleus

Opens the Door to Plausibility of Boundary Conditions and Cell / Organ GEOMETRY
having a significant role in the picture of metabolism, pathology, morphogenesis, and
more complex processes (learning, auto-immune recognition, intelligence…)

Opens the Door to Some Really Bizarre (from the Classical Perspective) Possibilities
of Influence and Communication in the Organic World…

MJD 34 16-02-07 2:41 PM

5.3
Convergent Streams of Evidence and Theory

Microtubules as Computational (CA) Networks
(Rasmussen)

MT as Information Processing Networks
(Koruga, Hameroff, Penrose)

MT as Cytoskeletal Regulators of Form and Function
(Established cell biology)

MT as Quantum Lasers
(Del Guidice, Vitiello, Yasue)

MT as Quantum Antennae
(Pitkänen)

Nonvanishing Vacuum Gauge Current (EM or Z0 or Both) BE Condensates
Wormholes serve as conduits between spacetime sheet of surrounding water
(Debye layer) and spacetime sheet of the MT, protein, DNA.

MJD 35 16-02-07 2:41 PM

5.4
Additional transparencies from earlier talks

MT structure

Dimer polarities

MT cellular automata models

MJD 36 16-02-07 2:41 PM

5(a)

MJD 37 16-02-07 2:41 PM

6. Experimental Foundations – Neurons and Nanoscopes
6.1
Objective
Study real-time changes in:
neuron topology
dendritic growth and interaction
boundary behavior
cytoskeletal (MT) geometry

based upon modulation of electromagnetic fields
applied within the cell culture environment

Approach
Cell cultures (neuronal, glial) observed through Atomic Force Microscopy
Construction of controlled growth and EMF measurement apparatus

Environment
Nanoscope III SPM with AFM, Bioscope

MJD 38 16-02-07 2:41 PM

6.2
Atomic Force Microscopy (AFM)
Nanoscope-III Multimode AFM with AS-12 “E” Scanner

Range: X-Y 10µm by 10µm Z 2.5µm

(1) Contact Mode
Silicon Nitride Cantilever
Force (or Spring) Constants 0.58, 0.32, 0.12, 0.06 N/m*
Nominal Tip Radius of Curvature 20 - 60nm
Cantilever Lengths 100 & 200µm
Cantilever Configuration V-shaped

(2) Tapping Mode
Silicon Cantilever
Force (or Spring) Constant 20 - 100 N/m
Resonant Frequency 200 - 400kHz
Nominal Tip Radius of Curvature 5 - 10nm
Cantilever length 125µm

MJD 39 16-02-07 2:41 PM

Figs. 6.1 – 6.3 Hand-drawn AFM transparencies
or
Slides (set 1; from Park Scientific)

MJD 40 16-02-07 2:41 PM

6.3
Neural Imaging
XR1 Xenopus Retinal Glial Cells

Preparation: (6c)
ECL (entactin, collagen, and laminin) treated glass cover slips
Constant 60% L15 buffer.

Imaging on:
Nanoscope III with 10µm2 Scanner and with Fluid Cell
Bioscope with Axiovert 135 Zeiss inverted optical microscope
(@ Lab of E. Henderson, Iowa State, assistants M. Galardi, C. Mosher)

Planned objectives:
Obtain large set of AFM cell images
Obtain confocal images of MT network (re: Henderson AFM-Confocal Microscope)
Extract MT feature maps
Characterize MT network geometries
Modulate cell cultures with variable EMF applied in-vitro

MJD 41 16-02-07 2:41 PM

Figs. 6.4 – 6.9
Transparency images of Neurons from Bioscope work (MG, Iowa)

MJD 42 16-02-07 2:41 PM

6.4
A much better quality set of images

[from http://www.bioforcelab.com/biotech/figs.html]
Live and fixed Xenopus laevis retinal glial XR1 cell imaged by AFM. High pass filtered contact height mode (A) and TappingMode
(B) images (living cell). (C) is deflection mode image of cell after fixation. (D) shows the same cell imaged by scanning laser confocal
microscopy after staining of f-actin with rhodamine-phalloidin. There is a strong correlation between fiber-like features in the AFM
image and actin filaments in the confocal image. Scale bar = 10um. (6c)

MJD 43 16-02-07 2:41 PM

6(a)
Notes about cell cultures:

Original plans:

Established clonal cell line, PC-12, originally derived from a rat adrenal pheochromocytoma []. PC-12 cells exhibit
many characteristics of neural cells and have been used extensively as a model system for neurobiological and
neurochemical studies. These cells transport, store, and release the neurotransmitters norepinephrine and dopamine
[] and express sodium action potentials []. They are responsive to nerve growth factor (NGF), a 130 kD protein
which arrests the mitotic process and causes the cells to extend long neuronal processes (the differentiated
phenotype) []. Removal of NGF causes the cells to revert to the proliferative phenotype.

Stock cultures maintained in T-25 flasks in D-MEM/F-12 medium supplemented with 10% horse serum, 5% fetal
bovine serum, and antibiotics in a water-saturated, 5% CO2 atmosphere. For AFM experiments the cells will be
trypsinized and seeded at known densities onto circular (12 mm diameter) microporous polycarbonate membranes
in special culture dishes (Costar Snapwell Transwell inserts). The membranes are treated to promote cell
attachment and growth. If differentiated cells are required, the D-MEM/F-12 medium will be supplemented with
2.5S NGF (the active subunit) at a concentration of 50 ng/ml.

For AFM experiments using live cells, the membranes will be removed from the inserts, backed with a 12 mm
round glass coverslip, and mounted in a perfusion chamber for imaging as described below. The cells can also be
fixed on the membranes using standard procedures for electron microscopy and imaged as dry preparations.
Presently this is accomplished using fixation in 2.5% glutaraldehyde in 0.1 M sodium cacodylate buffer at pH 7.2,
progressive dehydration in ethyl alcohol, and air drying from hexamethyldisilazane. The fixed membranes will be
detached from the inserts and taped to the magnetic puck for AFM imaging of membrane features and cytoskeletal
structures.

MJD 44 16-02-07 2:41 PM

6(b)
For comparative purposes some experiments will utilize a patented human neuronal cell line, hNT, available from
Stratagene Cloning Systems, Inc. These cells express different neuronal markers and receptors than PC-12 cells
(4,5). They will be cultured as stock NT2 precursor cells and differentiated to the hNT neuronal phenotype with
NGF as described for PC-12 cells. It is felt that the use of established immortal cell lines in lieu of primary
neuronal cultures offers several advantages for these studies. First, a ready supply of pure cell types can be
maintained at relatively low cost. Second, the differentiated phenotypes share several significant large-scale
structural and physiological characteristics with primary neurons; these basic similarities can reasonably be
expected to extend to the nanoscale level. In addition, the ability to control neurite outgrowth (axon-like
extensions) by treatment of the proliferative cells with NGF offers the possibility of producing synaptic
connections with a variety of target cells or with one another (3). This may be a useful feature for experiments
in which the properties of large synaptodendritic fields are to be investigated. Part of this study will investigate
methods for controlling the formation of these multicellular structures using the differentiable cell lines and NGF.

AFM Studies of Live Cells (Perfusion Chamber Studies)

In order to study dynamic changes in the structural features of cultured neuronal cells as a function of their
chemical environment, live cells grown on polycarbonate membranes as described above will be mounted in the
glass perfusion chamber provided by Digital Instruments for use with the Nanoscope. The coverslip-backed
membrane forms the floor of a closed flow-through cell which provides for the mounting of the AFM scanning
tip within the chamber itself thereby allowing the cells to be imaged in physiological solutions. This chamber will
form part of an open-ended system (similar to an HPLC flow line) through which HEPES-buffered culture
medium maintained at 37 oC and pH 7.4 will be pumped. This system will allow the cells to be exposed to
programmed alterations in medium constituents, e.g., ionic concentrations, and simultaneously scanned to record
changes in cell structure.

MJD 45 16-02-07 2:41 PM

6(c)
XR1 glial (Xenopus retinal ganglion) cells were grown in culture according to the protocol of Sakaguchi, et al.
(56, 55). Briefly, cells are harvested from tissue culture flasks and resuspended in culture media, then plated onto
a modified 60 mm culture dish which housed a 30 mm round glass cover slip (in some cases cells were grown on
free coverslips). The glass cover slip was pre-treated with ECL (entactin, collagen, and laminin) which promotes
flattening and adherence of the cells to the surface. Cultures were incubated at room temperature in ambient
atmosphere. Prior to imaging the cells, the culture media was gently aspirated from the preparation and replaced
with sufficient protein-free 60% L15 media to cover the cells. For experiments with fixed cells a solution of 4%
paraformaldehyde in 0.1M phosphate buffer (pH 7.3) was added, the sample was washed three times, and the
cells were stained with rhodamine-phalloidin for 30 to 60 minutes in the dark 25, 55).

For live cell work the petri dish was transferred to a rigid sample holder having a small aperture for optical
viewing. A triangular 200 µm long, 20 µm wide cantilever with pyramidal tip was mounted in the BioScope fluid
cell holder, positioned in close proximity to the sample (~50 µm) and engaged automatically. All AFM images
were taken in 60% L15 buffer. After fixing and labeling with rhodamine-phalloidin the sample was rinsed with
phosphate buffered saline (PBS) and imaged with the confocal microscope. Bright field images were acquired
using a fiber optic light source reflected from a 45° one-way mirror mounted on the scanning piezo.
Non-confocal epifluorescence images were generated by conventional optics. Optical data were captured with
an integrating CCD camera and stored in digital format on a Macintosh IIci computer using NIH Image
software (version 1.55) and a frame grabber board (Data Translation, Inc., Marlboro, MA).

MJD 46 16-02-07 2:41 PM

7. QNET : Quantum Networks
and the
CLANS : Cellular Local Area Nets
7.1
Objective

Computer simulation of network-like growth at multiple (2+) scales

Modeling quantum-like field behavior and soliton-like wave propagation
through constrained geometries (synapto-dendritic spaces)

Modeling boundary/topology-driven discontinuities and coherence as
predicted (or conjectured) by TGD and generic TD

Creation of a tool by which to search for interesting behaviors observed in
AFM and Confocal Experiments, and by which to refine a mathematical model
of the cellular dynamics of real biology

MJD 47 16-02-07 2:41 PM

7.2
Approach
PC-based programs, C/C++, MATLAB

Starting from platform of fractal, CA, and neural-network-like algorithms

Incorporation of CSP parallel processor paradigm:

ρ0
σ2.1
ρ2

σ3.1
σ1.1
ρ1 ρ3
σ1.2

MJD 48 16-02-07 2:41 PM

Figs. 7.1 – 7.3
Sketches (hand-drawn transparencies) and GEO / CELL programs

Figs. 7.4 – 7.6
From thesis – Figs. 2.5 (QCAM Configuration), 2.6 (QCAM Clan in Action),
and 2.10 (X-operator and multiple regions of pfocess network)

MJD 49 16-02-07 2:41 PM

8. New Experimental Approaches and Tools
8.1

Controlled Growth of Cell Cultures

Synthetic Neural Networks

Micro-Machined Electromagnetic Arrays

AFM, Optical and Confocal Microscopy Real-Time

MFM and Magneto-Optic Scanning

Continuous Observation in Three Modes (AFM, Optical, Magnetic)
Of Defined Cellular Topologies Exposed to Differentiable EMF Patterns

MJD 50 16-02-07 2:41 PM

8.2
Controlled-Growth Geometries of Cell Cultures

Goals
Long-term cultures
Self-assembled monolayers
Defined Pathways
Neuronal axon and dendrite polarities
Functional synapses
Regulated populations for analysis of transmitter and ion uptake levels

Methods
Chemical and UV Lithography Preparation

EDA (N-2-Aminomethyl-3-aminopropyl trimethoxysilane)
DETA (Trimethoxysilyl propyldiethyylenetriamine)
PEDA, TMA, CL, BIPY
Surface preps with PL (Poly(L-Lysine) and HS (Heparin sulfate glycosaminoglycan)

Significant pioneering advances by J. Hickman & D. Stenger (NRL)

MJD 51 16-02-07 2:41 PM

8.3
Micro-machined or SLM-Controlled Arrays for Controlled-Geometry EMF

EDA/PETA Treated
Growth Substrate with
Adhesive / Repulsion
Regions Lithographed

Electromagnetic elements
arranged in configuration
specific to the experiment

(R, Bi)3(Fe, Ga)5012
array employed as sensor
both below and above the
cell culture apparatus

MJD 52 16-02-07 2:41 PM

8.4
Imaging with AFM and Confocal Instrumentation

[from http://www.bioforcelab.com/biotech/figs.html] An integrated optical-atomic force microscope.
(A) Combined inverted optical microscope (Axiovert 135, Zeiss) and MultiMode AFM (BioScope,
Digital Instruments). (B) Optical and AFM images can be obtained simultaneously. This is possible
because of the coaxial arrangement of the AFM scanner and the objective lens of the optical
microscope.

MJD 53 16-02-07 2:41 PM

8.5

MFM and Magneto-Optic Scanning

MFM an established technology, but limited by AFM architecture

MFM prevents simultaneous Tapping-Mode AFM

Fe-Ga Magneto-optic thin-films could open a new dimension for
measuring fields in such experiments as are proposed:

EMF source apparatus

Cell culture ambient environment

MJD 54 16-02-07 2:41 PM

8.6
General composition of MODE thin-film wafers

(R, Bi)3(Fe, Ga)5012

R = Y, Lu, Pr, Gd, Tm, Yb, Er, Ho, Dy, Tb, Eu

Process
grown by epitaxial layering
Bi2O3-PbO-B2O3 solvent and garnet-forming oxides,
@ 940-1108 K temperature.

General MO characteristics
Saturation magnetization µMo = 0 … 1000G
Specific Faraday Rotation ΘF = 2.3 grad/µm
Absorption Coefficient α = 0.35 … 0.40 dB//µm
Max. domain wall velocity V = 200 … 2800 m/s
Coercivity < 0.1 Oe
MO Figure of Merit Ψ = 2ΘF/α > 10 grad/dB
Lattice parameter ≈ 1.25 nm

MJD 55 16-02-07 2:41 PM

8.7
Some Images Produced with MagVision Scanner Prototype
(PAL Video Winnov VIDEUM PC Video Board (ISA bus)

MJD 56 16-02-07 2:41 PM

8.8
MODE Scanner Testbed (Top View)

Rails
Scanner Carriage

Adjustable Rail Spacers
SampleRetainer Scanner
Sample Bed

Drive Assembly

Motor

Drive Chain

Sample Retainer
Scanner I/O Cable Drive Control Cable
Chain Retainer/Pulley

MJD 57 16-02-07 2:41 PM

8.9
MODE Scanner Testbed (End View)

Rail Spacer Assembly
Scanner Carriage

Scanner Unit Sample

Sample Bed (Frame Base) Scanner I/O Cable

MJD 58 16-02-07 2:41 PM

8(a)

MJD 59 16-02-07 2:41 PM

9. Recapitulation and Conclusions
Following a particular line of reasoning has required opening several doors, often
simultaneously, and peering into different rooms at the same time…

Topological
Geometro- Solitons in
Dynamics 1+D and
(Classical/ Stability
Quantum)
Magneto-
Optics and
SPM
MT and
Membrane
Dynamics
Complexity
P-Adic and
Numbers & Automata
LengthScales

MJD 60 16-02-07 2:41 PM

CREDITS

I. Bogolubsky (LCTA, JINR, Dubna)
L. Brizhik (ITP, Kiev)
J. Chen (Grad student, BME)
A. Chernovenkis (MODIS)
R. Freer (Commonwealth Biotechnologies)
M. Gilardi (Lab Assistant)
E. Henderson (Iowa State)
S. Japee (Grad student, BME)
M. Pitkanen (Univ. of Helsinki)
V. Sanyuk (People’s Friendship Univ., Moscow)
P. Werbos (NSF)

MJD 61 16-02-07 2:41 PM

Tdbasicsem

More Related Content

What's hot (18)

Similar to Tdbasicsem (20)

More from martindudziak (20)

Tdbasicsem